The goal of this proposal is to develop and test an innovative interventional radiology technique for detecting and guiding biopsies of breast lesions in women with radiographically-dense and/or fibrocystic breasts. The use of a tumor-specific tracer (18F-Fluorodeoxyglucose [FDG]) which produces penetrating radiation is to be combined with a new imaging modality (positron emission mammography [PEM]) and a novel method of calculation of stereotactic coordinates to create this unique diagnostic procedure. An estimated 25% of women receiving mammograms have radio-dense breasts; making lesion detection difficult or impossible due to enhanced attenuation of x-rays, and similarities in the densities of lesions and dense normal tissues. This number is certain to rise in light of the recent recommendation by the American College of Radiology that women over the age of 40 and at average risk for breast cancer start regular mammographic screening, since radiographically-dense breasts are most common in women under the age of 50. A number of studies with PET have demonstrated the good tumor-to-background ratio achievable with FDG in breast cancer. The limited resolution and detection sensitivity inherent in most current generation PET scanners, however, limits the minimum size of lesions that can be reliably detected with FDG-PET scanners to approximately 10 mm in diameter. The advent of a new class of dedicated, high-resolution, high-sensitivity breast imagers (PEM) has made the detection of small lesions in the breast feasible. While the good sensitivity (~90%) exhibited by FDG in detecting palpable lesions has led some researchers to propose utilizing FDG-PEM scanning as a method for non-invasively diagnosing breast cancer, it is unlikely that the information obtained solely from these images can replace more definitive information gained from tissue samples acquired through biopsy. In this proposal the investigators describe the steps for development of a novel approach to guiding stereotactic percutaneous core biopsy of radiotracer-avid lesions using FDG-PEM images when standard mammographic methods are non-optimal. In addition to methods for rejection of scatter and random coincidences, a unique procedure for verifying biopsy needle positioning will be developed and optimized. Finally, the PEM-guided stereotactic biopsy technique will be evaluated in a pre-clinical trial utilizing a small group of subjects to determine the effectiveness of this method for obtaining tissue samples from breast lesions. It is proposed that these initial experiments will aid in defining the role of this novel technique in the diagnosis of women with indeterminate mammograms.